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V.A. DePass, N. McLaren, R. Ayala-Luga, C. Downs, J.E. Richards, S.E. Moroi; Association between MDR1 Polymorphisms in Exon 26 and Filtration Bleb Results After Trabeculectomy with Mitomycin C . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3306.
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Purpose: To determine if sensitivity to mitomycin C (MMC), a chemotherapeutic drug used to enhance the success of filtration surgery in patients with glaucoma, is associated with single nucleotide polymorphisms (SNPs) in p-glycoprotein, which is encoded by the multidrug resistance 1 gene (MDR1). Methods: We reviewed the medical records of sixteen subjects who underwent trabeculectomy with MMC. Patient demographics, ocular diagnoses, pre- and post-operative intraocular pressure (IOP), and surgical information were obtained. Each subject enrolled in an IRB-approved clinical research study and provided a blood sample. DNA was extracted from whole blood and exon 26 of the MDR1 was sequenced. Results: There were nine females and seven males, who had an age range of 31 to 80 years at the time of surgery. Glaucoma diagnoses included primary open-angle (n=10), juvenile (n=3), uveitic (n=2), or normal tension glaucoma (n=1). Twelve subjects were classified as MMC "sensitive", defined as hypotony without the use of glaucoma medications; and four were MMC "resistant", defined as bleb or filter failure, bleb scarring, or resumption of glaucoma medications within two months after trabeculectomy. In addition, the following complications were considered: cataract progression, suture lysis, needling, conjunctival wound leak, flat chamber, hyphema, iridocorneal adhesion, corneal edema, dellen, epithelial defect, choroidal detachment, bleb encapsulation, blebitis, endophthalmitis, and bleb leak. At exon 26, nucleotide 3396, of MDR1, all sixteen subjects had the homozygous common base. At exon 26, nucleotide 3435, ten of sixteen subjects demonstrated the homozygous C nucleotide; three were MMC resistant and seven were MMC sensitive. Three had demonstrated the homozygous T nucleotide, all of which were MMC sensitive. Three of the sixteen subjects demonstrated the heterozygous C/T nucleotide; two were MMC sensitive and one was MMC resistant. Conclusions: In our preliminary results, we found no trend for an association between the SNPs in exon 26 of MDR1 and sensitivity to MMC. More genetic variations should be considered beyond SNPs in exon 26 of MDR1, and other related genes affecting cellular sensitivity to MMC. We are enrolling more subjects to test our hypothesis of a genetic component to sensitivity to MMC.
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